ABSTRACT: Coastal shellfish are being threatened by several drivers acting at multiple temporal and spatial scales, including fishing, climate, and globalization of markets. We evaluated large-scale and long-term combined effects of fishing, climate, and economic variables on 2 congeneric clams that inhabit sandy beaches of the Pacific (Mesodesma donacium) and the Atlantic (M. mactroides) in South America. Bioeconomic and climatic variables, such as coastal sea surface temperature anomalies (SSTA) and broad-scale climatic indices (Pacific Decadal Oscillation and Atlantic Multidecadal Oscillation), were related to variations in clam populations in a differential way according to latitude and oceanographic features. For M. donacium, the nature and sign of the relationships between landings and explanatory predictors markedly differed between bioclimatic units. El Niño Southern Oscillation events negatively affected landings in Peru and northern Chile, whereas landings increased in southern Chile and showed a positive correlation with increasing SSTA, suggesting a positive effect at the southernmost edge of the species distribution. Long-term trends in the abundance of M. mactroides were related to fishing intensity and SSTA. As anticipated by basic economic theory, deficit of supply relative to demand, exacerbated by very low harvesting costs, pushed the price up and has driven these clam species to levels close to extinction (anthropogenic Allee effect). The lack of response of the stocks to long-term closures suggests that these systems exceeded critical thresholds (tipping points). Information on early warnings of tipping points is needed to help manage coastal shellfisheries that are increasingly threatened by long-lasting and large-scale stressors.